Ghadersohi Ali, Odunsi Kunle, Zhang Shaozeng, Azrak Rami G, Bundy Brian N, Manjili Masoud H, Li Fengzhi
Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
Int J Cancer. 2008 Sep 15;123(6):1376-84. doi: 10.1002/ijc.23667.
We have previously shown that ovarian tumors express prostate-derived Ets transcription factor (PDEF). However, the precise role of PDEF in the prognosis of ovarian cancer is unknown. In our study, we report for the first time that expression of PDEF in tumor lesions of patients with ovarian cancer is associated with favorable prognosis. Evaluation of samples from 40 patients with ovarian cancer showed that early stage (IA) and borderline (IIB, III) ovarian tumors expressed higher levels of PDEF mRNA and protein and lower levels of survivin compared to late stage ovarian tumors (IIIC and IV, p < 0.05). Normal ovarian tissues expressed the highest levels of PDEF mRNA and protein when compared to tumor tissues (p < 0.05). A Log-Rank test showed that overall survival of patients with PDEF-positive and survivin-negative ovarian tumors was significantly longer than those with PDEF-negative and survivin-positive tumors (p < 0.01). Forced expression of PDEF in PDEF-negative ovarian tumor cells inhibited tumor cell growth, induced apoptosis, downregulated survivin expression and its promoter activity. Furthermore, treatment of ovarian cancer cells with vitamin D or a selenium compound resulted in re-expression of PDEF, downregulation of survivin, induction of apoptosis and inhibition of tumor cell growth when compared to untreated controls (p < 0.05). Together, these observations showed an inverse correlation between PDEF and survivin expression and suggested that increased PDEF expression along with reduced survivin was associated with prolonged survival of patients with ovarian cancer.
我们之前已经表明,卵巢肿瘤表达前列腺源性Ets转录因子(PDEF)。然而,PDEF在卵巢癌预后中的具体作用尚不清楚。在我们的研究中,我们首次报道,卵巢癌患者肿瘤病灶中PDEF的表达与良好的预后相关。对40例卵巢癌患者样本的评估显示,与晚期卵巢肿瘤(IIIC和IV期,p<0.05)相比,早期(IA期)和交界性(IIB、III期)卵巢肿瘤表达更高水平的PDEF mRNA和蛋白,以及更低水平的生存素。与肿瘤组织相比,正常卵巢组织表达最高水平的PDEF mRNA和蛋白(p<0.05)。对数秩检验显示,PDEF阳性且生存素阴性的卵巢肿瘤患者的总生存期明显长于PDEF阴性且生存素阳性的肿瘤患者(p<0.01)。在PDEF阴性的卵巢肿瘤细胞中强制表达PDEF可抑制肿瘤细胞生长、诱导凋亡、下调生存素表达及其启动子活性。此外,与未处理的对照相比,用维生素D或硒化合物处理卵巢癌细胞导致PDEF重新表达、生存素下调、诱导凋亡并抑制肿瘤细胞生长(p<0.05)。总之,这些观察结果表明PDEF与生存素表达呈负相关,并提示PDEF表达增加以及生存素减少与卵巢癌患者的生存期延长有关。